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871.
Timothy E. Machonkin Patrick L. Holland Kristine N. Smith Justin S. Liberman Adriana Dinescu Thomas R. Cundari Sara S. Rocks 《Journal of biological inorganic chemistry》2010,15(3):291-301
2,6-Dichlorohydroquinone 1,2-dioxygenase (PcpA) from Sphingobium chlorophenolicum ATCC 39723 is a member of a class of Fe(II)-containing hydroquinone dioxygenases that is involved in the mineralization of
the pollutant pentachlorophenol. This enzyme has not been extensively characterized, despite its interesting ring-cleaving
activity and use of Fe(II), which are reminiscent of the well-known extradiol catechol dioxygenases. On the basis of limited
sequence homology to the extradiol catechol dioxygenases, the residues ligating the Fe(II) center were originally proposed
to be H159, H227, and E276 (Xu et al. in Biochemistry 38:7659–7669, 1999). However, PcpA has higher sequence homology to a newly reported, crystallographically characterized zinc metalloenzyme that
has a similar predicted fold. We generated a homology model of the structure of PcpA based upon the structure of this zinc
metalloenzyme. The homology model predicts that the tertiary structure of PcpA differs significantly from that of the extradiol
dioxygenases, and that the residues ligating the Fe(II) are H11, H227, and E276. This structural model was tested by mutating
each of H11, H159, H227, and E276 to alanine. An additional residue that is predicted to lie near the active site and is conserved
among PcpA, its closest homologues, and the extradiol dioxygenases, Y266, was mutated to phenylalanine. Of these mutants,
only H159A retained significant activity, thus confirming the active-site location predicted by the homology-based structural
model. The model provides an important basis for understanding the origin of the unique function of PcpA. 相似文献
872.
Adriana Alvaro Roser Rosales Lluís Masana Joan-Carles Vallvé 《The Journal of nutritional biochemistry》2010,21(6):518-525
Several transporter proteins regulate intestinal cholesterol absorption. Of these proteins, NPC1L1 is a major contributor to this process. Fatty acids (FAs) modulate cholesterol absorption by a mechanism that remains unknown. We evaluate the effect of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) on the expression of NPC1L1 and others proteins associated with cholesterol absorption (SR-BI, ABCG5, ABCG8, ABCA1, CAV-1, ANX-2) in human enterocytes in vitro. The role of SREBPs, PPARs, LXR and RXR in this process was also investigated. Caco-2/TC-7 enterocytes were incubated for 24 h with a wide range of concentrations of FA–bovine serum albumin (50–300 μM). Gene expression was analyzed by quantitative real-time PCR. The NPC1L1 protein present in enterocyte membranes was analyzed using Western blot. NPC1L1 mRNA levels were reduced 35–58% by the n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (P<.05). Linoleic acid (n-6), palmitic acid and oleic acid did not affect NPC1L1 mRNA expression. ABCA1 mRNA levels were reduced 44–70% by n-6 arachidonic acid and 43–55% by n-3 EPA (P<.05). LXR and LXR+RXR agonists decreased NPC1L1 mRNA expression by 28% and 57%, respectively (P<.05). A concentration of 200 μM of EPA and DHA decreased NPC1L1 protein expression in enterocyte membranes by 58% and 59%, respectively. We have demonstrated that the PUFAs n-3 EPA and DHA down-regulate NPC1L1 mRNA expression. In addition, PUFAs also down-regulate NPC1L1 protein expression in enterocyte membranes. LXR and RXR activation induced a similar repression effect. The lipid-lowering effect of n-3 PUFAs could be mediated in part by their action at the NPC1L1 gene level. 相似文献
873.
874.
Votto AP Domingues BS de Souza MM da Silva Júnior FM Caldas SS Filgueira DM Clementin RM Primel EG Vallochi AL Furlong EB Trindade GS 《Biological research》2010,43(4):429-437
Onion (Allium cepa) is being studied as a potential anticancer agent, but little is known regarding its effect in multidrug resistance (MDR) cells. In this work, the cytotoxicity of crude onion extract (OE) and fractioned extract (aqueous, methanolic and ethyl acetate), as well as some onion compounds (quercetin and propyl disulfide) were evaluated in Lucena MDR human erythroleukemic and its K562 parental cell line. The capacity of OE to induce apoptosis and/or necrosis in these cells, the possible participation of oxidative stress and DNA damage were also assessed. Similar sensitivities were obtained for both tumoral cells, however only OE caused significant effects in the cells. In K562 cells, a significant increase of apoptosis was verified while the Lucena cells experienced a significant increase of necrosis. An antioxidant capacity was verified for OE discarding oxidative damage. However, OE provoked similar significant DNA damage in both cell lines. Thus, the OE capacity to overcome the MDR phenotype suggests anti-MDR action of OE. 相似文献
875.
Adriana Dinescu Teresa R. Brown Thomas R. Cundari 《Biochemical and biophysical research communications》2010,400(4):511-516
Experimental kinetics and computational modeling of human glutathione synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (<0.7 and 0.3%, respectively, versus wild-type hGS). However, G371V retains ∼13% of the activity of wild-type hGS. With respect to G-loop:A-loop interaction in hGS, mutations at Gly369 and Gly370 decrease ligand binding and prevent active site closure and protection. This research indicates that Gly369 and Gly370 have essential roles in hGS, while Gly371 has a lesser involvement. Implications for glycine-rich ensembles in other phosphate-binding enzymes are discussed. 相似文献
876.
Several species of stenodermatine bats congregate in large numbers at collpas in southeastern Peru to drink water. We conducted the first experimental tests of preference for collpa water by representative bats. Artibeus species preferred mineral-rich collpa water over water from other sources, supporting the hypothesis that they seek resources (especially sodium) at collpas. 相似文献
877.
878.
879.
Ofir Picazo Adriana Becerril-Montes Delia Huidobro-Perez Luis M. Garcia-Segura 《Cellular and molecular neurobiology》2010,30(5):675-682
17α-Ethynylestradiol (EE2), a major constituent of many oral contraceptives, is similar in structure to 17β-estradiol, which
has neuroprotective properties in several animal models. This study explored the potential neuroprotective actions of EE2
against kainic and quinolinic acid toxicity in the hippocampus of adult ovariectomized Wistar rats. A decrease in the number
of Nissl-stained neurons and the induction of vimentin immunoreactivity in astrocytes was observed in the hilus of the dentate
gyrus of the hippocampus after the administration of either kainic acid or quinolinic acid. EE2 prevented the neuronal loss
and the induction of vimentin immunoreactivity induced by kainic acid at low (1 μg/rat) and high (10–100 μg/rat) doses and
exerted a protection against quinolinic acid toxicity at a low dose (1 μg/rat) only. These observations demonstrate that EE2
exerts neuroprotective actions against excitotoxic insults. This finding is relevant for the design of new neuroprotective
estrogenic compounds. 相似文献
880.
Cláudia Funchal Carlos Augusto Souza Carvalho Tanise Gemelli Andressa S. Centeno Robson Brum Guerra Mirian Salvador Caroline Dani Adriana Coitinho Rosane Gomez 《Cellular and molecular neurobiology》2010,30(7):1135-1142
Organotellurium compounds have been synthesized since 1840, but pharmacological and toxicological studies about them are still
incipient. Therefore, the objective of this study was to verify the effect of acute administration of the organochalcogen
3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of oxidative stress in the brain of 30-day-old rats. Animals
were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 μg/kg body weight) and sacrificed
60 min after the injection. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl.
Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD),
nitric oxide (NO) formation, and hydroxyl radical production were measured in the brain. The organotellurium enhanced TBARS
in the cerebral cortex and the hippocampus, and increased protein damage (carbonyl) in the cerebral cortex and the cerebellum.
In contrast, the compound provoked a reduced loss of thiol groups measured by the sulfhydryl assay in all the tissues studied.
Furthermore, the activity of the antioxidant enzyme CAT was reduced by the organochalcogen in the cerebral cortex and the
cerebellum, and the activity of SOD was inhibited in all the brain tissues. Moreover, NO production was increased in the cerebral
cortex and the cerebellum by this organochalcogen, and hydroxyl radical formation was also enhanced in the cerebral cortex.
Our findings indicate that this organotellurium compound induces oxidative stress in the brain of rats, corroborating that
this tissue is a potential target for organochalcogen action. 相似文献